The goal of this proposal is the study of the deregulation of immune responses following in vivo chronic B cell stimulation. In the event that an effective measure will be obtained to eliminate retroviruses causing acquired immunodeficiency syndrome, (AIDS) there will still remain the problem of how to redress B cell deregulation. Most AIDS patients present with gross abnormalities in B cell regulation. We propose to study the characteristics of chronic B cell deregulation. Preliminary evidence points to a dramatic decrease of the magnitude of the immune response to a thymic-dependent antigen, following chronic in vivo polyclonal B cell stimulation. We propose to study the regulatory mechanisms affected by chronic polyclonal in vivo B cell stimulation. This will be accomplished through the following specific aims: Specific aim #1: In vivo effects of chronic polyclonal B cell stimulation on the immune responses to thymic-dependent and thymic-independent antigens. Specific aim #2: Analysis of the changes in the cellular sub-populations of lymphocytes following in vivo B cell chronic polyclonal activation. Specific aim #3: Analysis of changes in defined idiotypic antibody expression following B cell in vivo polyclonal activation. Specific aim #4: Studies on the alteration in B cell responses to bacterial antigens following in vivo B cell stimulation. Specific aim #5: Studies on the changes in viral disease susceptibility following chronic in vivo B cell polyclonal stimulation. The studies proposed above are designed to identify B cell regulatory changes following B cell chronic in vivo B cell stimulation. Furthermore, the rates of recovery of normal immune functions will be studied, leading to possible approaches to therapeutic procedures, in those diseases where patients present with B cell polyclonal activation.